Next generation sequencing (NGS) technologies can produce large volumes of human genome sequence data inexpensively. Carrier testing identifying individuals who carry one copy of a variant in a gene for a disease that requires two copies to be expressed is a prime candidate for clinical implementation of NGS technology. We will investigate the clinical implementation of carrier testing using whole genome sequencing to aid reproductive decision-making in adults. The study population will include women and their partners requesting pre-conception testing for cystic fibrosis (CF) carrier status, or other conditions. We propose three interrelated projects. In Project 1, we will conduct a Randomized Clinical Trial within the Kaiser Permanente Northwest (KPNW) health plan to test clinical implementation of whole genome sequencing and the integration of this screening within the electronic medical record (EMR), as well as measure outcomes from patient and physician perspectives. We will evaluate the comparative outcomes of adding genome sequencing versus usual care or versus a targeted genomic test panel. In Project 2, we will perform genome sequencing of the laboratory test samples, including validation and interpretation of the identified variants to identify actionable variants deemed worthy of reporting to doctors and patients. This will include using a Return of Results Committee (RORC). In Project 3, we will evaluate the ethical and psychosocial implications of expanded carrier screening for the return of carrier status and secondary findings from whole genome sequencing, and evaluate the downstream healthcare utilization and costs. This project will have a far-reaching impact and will inform discussions about the advantages and disadvantages of returning preconception carrier status results from whole genome sequencing. Carrier testing represents a high proportion of genetics services delivered, meaning this program can be readily translated to a large number of patients. Our focus on patients seeking preconception carrier status will allow us to rapidly assess the potential impact of using NGS for carrier status. Our access to real world patients and clinical settings will make our research broadly generalizable.